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Post-ART and No-ART Controllers Similar in Primary Infection Trial/Cure Trials
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21st International AIDS Conference (AIDS 2016), July 18-22, 2016, Durban, South Africa
Mark Mascolini
People with primary HIV infection who controlled viral replication spontaneously in the randomized SPARTAC trial were similar in many respects to people who controlled viremia after short-course antiretroviral therapy (ART) [1]. Nearly 8% of SPARTAC participants who did not start ART experienced a transient period of viral remission, a rate that did not differ significantly from post-ART controllers.
University of Oxford researchers and colleagues who performed this analysis noted that time to viral rebound after ART interruption is a central outcome of HIV cure trials. People with primary HIV infection are particularly interesting participants in such trials because their smaller HIV reservoirs and relatively preserved immune function raise chances that they will respond to cure strategies. The researchers underlined the importance of understanding spontaneous viral control in such trials among participants who do not receive the study intervention.
SPARTAC outcomes lend themselves to pinpointing differences between spontaneous and treatment-related viral control because the trial randomized people with primary infection to (1) up to 12 weeks of ART, (2) 12 to 48 weeks of ART, or (3) no therapy. In this analysis researchers compared untreated and treated HIV controllers who experienced remission while off ART. The researchers defined viral remission as (1) a viral load below 400 copies on at least two measures 16 weeks apart while off ART, and (2) a period of remission within 1 year of treatment interruption (if treated) or within 1 year of randomization (if untreated). All treated participants interrupted ART during the study period.
The study group included 80 people treated for up to 12 weeks, 86 treated for more than 12 weeks, and 126 who never started ART. Numbers (and proportions) of controllers in each group were 9 (11.3%), 16 (18.6%), and 10 (7.9%) (P = 0.06). Respective numbers and proportions without viral rebound at the end of follow-up were 1 (1.25%), 5 (5.8%), and 2 (1.6%). Only 1 person (in the no-ART group) had remission lasting fewer than 26 weeks, while similar proportions in the 12-week ART group (3.75%), the more than 12-week ART group (7.0%), and the no-ART group (5.6%) controlled viremia more than 104 weeks. Overall duration of remission did not differ significantly across the three groups (P = 0.22).
Median age was nonsignificantly older in the group treated for up to 12 weeks (40 years) than in the group treated more than 12 weeks (27.5 years) or the untreated group (32 years) (P = 0.33). The groups did not differ in proportions with 1 or more protective class I HLA alleles or proportions with the B*35:01 allele.
Compared with SPARTAC participants who did not control viremia, controllers had more favorable clinical characteristics at baseline. Controllers who took ART did not differ substantially from no-ART controllers in two baseline traits: CD4 count and total HIV DNA. But the no-ART group had a significantly lower baseline viral load than the group treated more than 12 weeks (about 2 versus 4 log10 copies/mL). The three controller groups did not differ significantly from each other in number or magnitude of CD8 responses to gag epitopes.
The researchers concluded that "a substantial proportion of untreated individuals with primary HIV infection experience periods of viral control." They urged colleagues to consider spontaneous remissions during primary infection to avoid overestimating the impact of interventions in treatment interruption studies.
References
1. Martin GE, Gossez M, Williams JP, et al. Post-treatment control or treated controllers? The impact of ART on time to viral rebound in recent seroconverters. 21st International AIDS Conference (AIDS 2016). July 18-22, 2016. Durban, South Africa. Abstract TUPEA011.
2. SPARTAC Trial Investigators, Fidler S, Porter K, Ewings F, et al. Short-course antiretroviral therapy in primary HIV infection. N Engl J Med. 2013;368:207-217. http://www.nejm.org/doi/full/10.1056/NEJMoa1110039
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